Authors :
Presenting Author: Mae Morton-Dutton, BA – Center for Brain Circuit Therapeutics, Department of Neurology, Psychiatry, and Radiology, Brigham and Women’s Hospital
John Archer, PhD – Department of Medicine – The University of Melbourne; Ellen Bubrick, MD – Center for Brain Circuit Therapeutics, Department of Neurology – Brigham and Women's Hospital; Xingui Chen, MD – Department of Neurology – Anhui Medical University; Gabriel Gonzalez-Escamilla, PhD – Department of Neurology – University Medical Center of the Johannes Gutenberg; Sergui Groppa, MD, PhD – Department of Neurology – University Medical Center of the Johannes Gutenberg University; Andreas Horn, MD, PhD – Center for Brain Circuit Therapeutics, Department of Neurology – Brigham and Women's Hospital; Panpan Hu, MD – Department of Neurology – Anhui Medical University; Yubao Jiang, MD – Department of Neurology – Anhui Medical University; Sara Lariviere, Postdoctoral Fellow – Center for Brain Circuit Therapeutics, Department of Neurology – Brigham and Women's Hosptial; Clemens Neudorfer, MD – Center for Brain Circuit Therapeutics, Department of Neurology – Brigham and Women's Hospital; John Rolston, MD, PhD – Center for Brain Circuit Therapeutics, Department of Neurology – Brigham and Women's Hospital; Frederic Schaper, MD, PhD – Department of Neurology – Brigham and Women's Hospital; Jinmei Sun, MD – Department of Neurology – Anhui Medical University; Yanghua Tian, MD – Department of Neurology – Anhui Medical University; Cristina Torres Diaz, MD – Department of Neurosurgery – Universitario de La Princesa; Kai Wang, MD, PhD – Department of Neurology – Anhui Medical University; Yingru Wang, Master – Department of Neurology – Anhui Medical University; Aaron Warren, PhD – Center for Brain Circuit Therapeutics, Department of Neurology – Brigham and Women's Hospital; Chunyan Zhu, MD – Department of Neurology – Anhui Medical University; Michael Fox, MD, PhD – Principal Investigator, Center for Brain Circuit Therapeutics, Department of Neurology, Brigham and Women's Hospital; Gong-Jun Ji, PhD – Department of Neurology – Anhui Medical University
Rationale:
Idiopathic generalized epilepsy (IGE) is a common form of epilepsy characterized by generalized-onset of tonic-clonic, absence, and/or myoclonic seizures and is increasingly conceptualized as a brain network disease. A better understanding of the brain networks involved in IGE could inform treatment strategies including (non)invasive brain stimulation. In this study, we test whether neuroimaging abnormalities in IGE map to a common brain network and whether they can inform network therapies such as deep brain stimulation (DBS).
Methods: We retrieved all published coordinates of brain abnormalities (atrophy or fMRI hyperactivity) associated with IGE compared to controls. We then computed the functional connectivity of the reported coordinates using the resting-state fMRI data of 652 controls (human connectome), a method termed "coordinate-network mapping." First, we tested if coordinates of IGE abnormalities map to a common brain network. Second, we determined the specificity of this network compared to coordinate networks in neurodegenerative disease or random coordinates. Third, we evaluated generalizability of this network to findings from (inter)ictal simultaneous EEG-fMRI studies including IGE or other epilepsies and to brain lesions causing focal seizures that generalize versus those that do not. Finally, we tested the therapeutic relevance of this network using two independent datasets of patients with generalized epilepsy receiving centromedian (CM)-DBS, by correlating network overlap of the stimulation site with the reduction of seizure frequency after DBS.
Results: Brain abnormalities in IGE are functionally connected to a common brain network despite being heterogeneously distributed in the brain. This IGE network included the somatomotor area, pre- and post-central gyri, superior temporal gyrus, operculum, insula, centromedian thalamus, posterior putamen, brainstem, and cerebellum. These connections are both sensitive (peak network overlap >85%) and specific (
pFDR< 0.05) compared to coordinate networks from neurodegenerative diseases or random coordinates. Regions identified as hyperactive using (inter)ictal simultaneous EEG-fMRI in IGE patients showed greater IGE network overlap compared to regions from other epilepsies (
p< 0.01). Brain lesions causing focal seizures that generalize showed greater IGE network overlap compared to lesions causing only focal seizures (
p< 0.01). Greater overlap of CM-DBS sites with the IGE network correlated with better seizure control after DBS (
r = 0.44,
p < 0.02).